Patrick D. McMullen
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View article: Out-of-State Acute Care Use Among Pediatric Medicaid Enrollees
Out-of-State Acute Care Use Among Pediatric Medicaid Enrollees Open
Importance For many US children, the nearest hospital may be out of state. Medicaid coverage differs by state, affecting access across state lines. Objective To evaluate the frequency of out-of-state acute care use for pediatric patients. …
View article: GPR143-Associated Ocular Albinism in a Hispanic Family and Review of the Literature
GPR143-Associated Ocular Albinism in a Hispanic Family and Review of the Literature Open
Background/Objectives: While ocular albinism (OA) is usually associated with reduced vision, nystagmus, and foveal hypoplasia, there is phenotypic variability in iris and fundus hypopigmentation. Hemizygous pathogenic/likely pathogenic (P/…
View article: Network Analysis to Define Pediatric Acute Care Regions in Wisconsin
Network Analysis to Define Pediatric Acute Care Regions in Wisconsin Open
Objective To pilot a system for deriving borders of pediatric regions, and to compare these to adult markets based on fit with pediatric utilization data. Study Setting and Design In this cross‐sectional study, we studied all acute care en…
View article: In vitro to in vivo extrapolation from 3D hiPSC-derived cardiac microtissues and physiologically based pharmacokinetic modeling to inform next-generation arrhythmia risk assessment
In vitro to in vivo extrapolation from 3D hiPSC-derived cardiac microtissues and physiologically based pharmacokinetic modeling to inform next-generation arrhythmia risk assessment Open
Proarrhythmic cardiotoxicity remains a substantial barrier to drug development as well as a major global health challenge. In vitro human pluripotent stem cell-based new approach methodologies have been increasingly proposed and employed a…
View article: A Case of Non-Syndromic Congenital Cataracts Caused by a Novel MAF Variant in the C-Terminal DNA-Binding Domain—Case Report and Literature Review
A Case of Non-Syndromic Congenital Cataracts Caused by a Novel MAF Variant in the C-Terminal DNA-Binding Domain—Case Report and Literature Review Open
The MAF gene encodes a transcription factor in which pathogenic variants have been associated with both isolated and syndromic congenital cataracts. We aim to review the MAF variants in the C-terminal DNA-binding domain associated with non…
View article: Integrating gene expression and splicing dynamics across dose-response oxidative modulators
Integrating gene expression and splicing dynamics across dose-response oxidative modulators Open
Toxicological risk assessment increasingly utilizes transcriptomics to derive point of departure (POD) and modes of action (MOA) for chemicals. One essential biological process that allows a single gene to generate several different RNA is…
View article: Ocular manifestations of <scp>CHARGE</scp> syndrome in a pediatric cohort with genotype/phenotype analysis
Ocular manifestations of <span>CHARGE</span> syndrome in a pediatric cohort with genotype/phenotype analysis Open
CHARGE syndrome is a rare multi‐system condition associated with CHD7 variants. However, ocular manifestations and particularly ophthalmic genotype–phenotype associations, are not well‐studied. This study evaluated ocular manifestations an…
View article: Impact of gene selection criteria on transcriptomic ontology-based point of departure estimates
Impact of gene selection criteria on transcriptomic ontology-based point of departure estimates Open
Apical effects are typically associated with changes in gene expression, which allows for the use of short- term in life transcriptomic studies to derive biologically relevant points of departure (POD). These methods offer cost savings ove…
View article: Assessing the basal gene expression of cancer cell lines for in vitro transcriptomic toxicology screening
Assessing the basal gene expression of cancer cell lines for in vitro transcriptomic toxicology screening Open
In vitro toxicology has used immortalized cancer cell lines as model human systems for decades. However, these cell lines pose problems in designing toxicity testing programs as they inherently do not represent normal human biology. There …
View article: Estimating provisional margins of exposure for data-poor chemicals using high-throughput computational methods
Estimating provisional margins of exposure for data-poor chemicals using high-throughput computational methods Open
Current computational technologies hold promise for prioritizing the testing of the thousands of chemicals in commerce. Here, a case study is presented demonstrating comparative risk-prioritization approaches based on the ratio of surrogat…
View article: NAM-based prediction of point-of-contact toxicity in the lung: A case example with 1,3-dichloropropene
NAM-based prediction of point-of-contact toxicity in the lung: A case example with 1,3-dichloropropene Open
Time, cost, ethical, and regulatory considerations surrounding in vivo testing methods render them insufficient to meet existing and future chemical safety testing demands. There is a need for the development of in vitro and in silico alte…
View article: Considerations for Improving Metabolism Predictions for In Vitro to In Vivo Extrapolation
Considerations for Improving Metabolism Predictions for In Vitro to In Vivo Extrapolation Open
High-throughput (HT) in vitro to in vivo extrapolation (IVIVE) is an integral component in new approach method (NAM)-based risk assessment paradigms, for rapidly translating in vitro toxicity assay results into the context of in vivo expos…
View article: Biological system considerations for application of toxicogenomics in next-generation risk assessment and predictive toxicology
Biological system considerations for application of toxicogenomics in next-generation risk assessment and predictive toxicology Open
There is increasing interest in using modern 'omics technologies, such as whole transcriptome sequencing, to inform decisions about human health safety and chemical toxicity hazard. High throughput methodologies using in vitro assays offer…
View article: A systematic approach to evaluate plausible modes of actions for mouse lung tumors in mice exposed to 4-methylimidozole
A systematic approach to evaluate plausible modes of actions for mouse lung tumors in mice exposed to 4-methylimidozole Open
The National Toxicology Program (NTP) reported that chronic dietary exposure to 4-methylimidazole (4-MeI) increased the incidence of lung adenomas/carcinomas beyond the normally high spontaneous rate in B6C3F1 mice. To examine plausible mo…
View article: The TTC Data Mart: An interactive browser for threshold of toxicological concern calculations
The TTC Data Mart: An interactive browser for threshold of toxicological concern calculations Open
Computational technologies hold promise for informing decisions on the use of thousands of chemicals in commerce that have little or no toxicological data. Threshold of Toxicological Concern (TTC) groups compounds based on the outcome of a…
View article: The role of fit-for-purpose assays within tiered testing approaches: A case study evaluating prioritized estrogen-active compounds in an in vitro human uterotrophic assay
The role of fit-for-purpose assays within tiered testing approaches: A case study evaluating prioritized estrogen-active compounds in an in vitro human uterotrophic assay Open
Chemical risk assessment relies on toxicity tests that require significant numbers of animals, time and costs. For the >30,000 chemicals in commerce, the current scale of animal testing is insufficient to address chemical safety concerns a…
View article: Identifying qualitative differences in PPARα signaling networks in human and rat hepatocytes and their significance for next generation chemical risk assessment methods
Identifying qualitative differences in PPARα signaling networks in human and rat hepatocytes and their significance for next generation chemical risk assessment methods Open
In this paper, we evaluate the PPARα signaling network in rats, examining transcriptional responses in primary hepatocytes exposed to a PPARα specific ligand, GW7647. These transcriptomic studies were complemented with ChIP-seq studies of …
View article: Addressing systematic inconsistencies between in vitro and in vivo transcriptomic mode of action signatures
Addressing systematic inconsistencies between in vitro and in vivo transcriptomic mode of action signatures Open
Because of their broad biological coverage and increasing affordability transcriptomic technologies have increased our ability to evaluate cellular response to chemical stressors, providing a potential means of evaluating chemical response…
View article: A Qualitative Modeling Approach for Whole Genome Prediction Using High-Throughput Toxicogenomics Data and Pathway-Based Validation
A Qualitative Modeling Approach for Whole Genome Prediction Using High-Throughput Toxicogenomics Data and Pathway-Based Validation Open
Efficient high-throughput transcriptomics (HTT) tools promise inexpensive, rapid assessment of possible biological consequences of human and environmental exposures to tens of thousands of chemicals in commerce. HTT systems have used relat…
View article: Assessing bioactivity-exposure profiles of fruit and vegetable extracts in the BioMAP profiling system
Assessing bioactivity-exposure profiles of fruit and vegetable extracts in the BioMAP profiling system Open
The ToxCast program has generated in vitro screening data on over a thousand chemicals to assess potential disruption of important biological processes and assist in hazard identification and chemical testing prioritization. Few results ha…
View article: An in vitro approach for prioritization and evaluation of chemical effects on glucocorticoid receptor mediated adipogenesis
An in vitro approach for prioritization and evaluation of chemical effects on glucocorticoid receptor mediated adipogenesis Open
Rising obesity rates worldwide have socio-economic ramifications. While genetics, diet, and lack of exercise are major contributors to obesity, environmental factors may enhance susceptibility through disruption of hormone homeostasis and …
View article: Strain-related differences in mouse lung gene expression over a two-year period of inhalation exposure to styrene: Relevance to human risk assessment
Strain-related differences in mouse lung gene expression over a two-year period of inhalation exposure to styrene: Relevance to human risk assessment Open
Both CD-1 and C57BL/6 wildtype (C57BL/6-WT) mice show equivalent short-term lung toxicity from exposures to styrene, while long-term tumor responses are greater in CD-1 mice. We analyzed lung gene expression from styrene exposures lasting …
View article: Evaluating opportunities for advancing the use of alternative methods in risk assessment through the development of fit-for-purpose in vitro assays
Evaluating opportunities for advancing the use of alternative methods in risk assessment through the development of fit-for-purpose in vitro assays Open
An evolving regulatory, scientific, and legislative landscape is driving a fundamental change in how chemical safety decisions are made. As we move to implement changes, regulatory agencies and industry are beginning to adopt tiered approa…
View article: Applying 'omics technologies in chemicals risk assessment: Report of an ECETOC workshop
Applying 'omics technologies in chemicals risk assessment: Report of an ECETOC workshop Open
Prevailing knowledge gaps in linking specific molecular changes to apical outcomes and methodological uncertainties in the generation, storage, processing, and interpretation of 'omics data limit the application of 'omics technologies in r…